Alpha- and flaviviruses as well as other arboviruses are transmitted in nature via bidirectional arthropod-vertebrate cycles. This continuous crossing of phylogenetic barriers requires greater viral adaptibility to divergent organismal environments than is required of other animal viruses. The long-term objective is to compare genetic, biochemical and regulatory factors which may differentially affect the interaction of togaviruses with cultured vertebrate and insect cells. Mutant clones of Aedes albopictus cells have been isolated which, in contrast to the parental line, are destroyed by Sindbis virus (SV), an alphavirus. As a corrollary, we are planning to isolate and characterize host range mutants of SV. In this way we hope to identify cellular and viral functions involved in cell injury. The mechanism by which ribavirin inhibits SV replication in A. albo cells but not in BHK cells, is under study. So is the further characterization of defective-interfering (DI) SV particles and genomes. Well-characterized DI particles of vesicular stomatitis virus are used as models for the study of regulatory events in the generation of DI genomes. Dengue-2 virus serves as the prototype flavivirus under investigation. Further details of transcription and translation remain to be worked out, mainly in vertebrate cells, in order to establish a frame of reference for comparative studies in mosquito cells.